The halophilic bacterium Vibrio vulnificus, also called "Lactose-positive Vibrio species" and Beneckea vulnifica in the medical literature, is found in marine and estuarine environments and is a recently recognized etiologic agent of severe wound infections and life-threatening septicemia and pneumonia in humans. The long-term objective of the research described in this application is to understand the pathogenesis of V. vulnificus-induced diseases well enough to aid the prevention and treatment of the diseases. The specific aim of the research described in the application is two-fold. First, to isolate and characterize lethal, capillary permeability-enhancing, cytolytic, and cytotoxic substances produced by the bacterium and, second, to evaluate the hypothesis that in vivo production of the toxin(s) is important in the pathogenesis of disease caused by the bacterium. After determining the growth conditions which are optimal for toxin production, the toxin(s) will be isolated in a homogeneous state and physicochemically characterized by application of biochemical and immunologic techniques. Studies to determine whether toxin production is important in the pathogenesis of disease caused by the bacterium will include: (i) determining whether active and passive immunization against the isolated toxin(s) protects mice against tissue damage and/or death following challenge with the bacterium, (ii) determining, by biological activity assays and by immunologic techniques, whether the toxin(s) is produced in vivo during the development of the infectious disease process in mice, (iii) comparing, by light and electron microscopy, the tissue damage produced in mice by the bacterium and by the isolated toxin(s), (iv) determining if parenteral administration of the isolated toxin(s) to mice enhances the virulence of challenge doses of the bacterium, and (v) determining whether the purified toxin(s) deleteriously affects the structure and/or function of isolated phagocytic cells obtained from the mouse and rabbit.